Expression of RAP1B is associated with poor prognosis and promotes an aggressive phenotype in gastric cancer

Abstract

Metastasis is the major cause of death among gastric cancer (GC) patients, and altered expression of Ras-related protein RAP1B is associated with cancer development. The present study assessed RAP1B expression ex vivo and the effect of hypoxia‑induced RAP1B overexpression on the promotion of the metastatic potential of GC cells in vitro. Immunohistochemistry was used to detect the expression of RAP1B and hypoxia‑inducible factor-1α (HIF-1α) in 178 GC tissue specimens. GC cell lines were used to assess the effects of hypoxia and RAP1B knockdown with RAP1B small interfering RNA (siRNA). Tumor cell viability was detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, invasion capacity was evaluated by a Transwell assay, and gene expression was determined by qRT-PCR and western blotting. The data showed that expression levels of RAP1B and HIF-1α proteins were high in the GC tissue specimens, and RAP1B expression was significantly associated with tumor-node-metastasis (TNM) stage and tumor size, while HIF-1α expression was significantly associated with TNM stage, Borrmann type and tumor differentiation. Moreover, RAP1B expression was associated with HIF-1α expression (r=0.547, P<0.001). The expression of RAP1B and HIF-1α proteins was associated with a shorter overall survival of patients according to the univariate analysis (log-rank test, P<0.01), and RAP1B expression and TNM stage were independent prognostic predictors in patients using a multivariate analysis (P<0.001). In vitro, hypoxia induced the invasion of GC cells and the expression of RAP1B and HIF-1α (P<0.05); whereas knockdown of RAP1B expression using siRNA inhibited the tumor cell invasion capacity even under hypoxic culture conditions (P<0.05). In conclusion, the protein expression of RAP1B and HIF-1α contributed to GC malignant behavior and poor prognosis. Future studies will evaluate whether targeting RAP1B expression can be used as a novel strategy to control GC or as a biomarker for prognosis prediction.

High Infiltration of Tumor-Associated Macrophages Influences Poor Prognosis in Human Gastric Cancer Patients, Associates With the Phenomenon of EMT

“… 26 We have previous shown expression of RAP1B is associated with poor prognosis and promotes an aggressive phenotype in gastric cancer. 27 However, whether or not infiltration of TAMs is involved in EMT of human GC needs further investigation.…”

OSeac: An Online Survival Analysis Tool for Esophageal Adenocarcinoma

“…Finally, to determine the performance of OSeac, three published EAC prognostic biomarkers were assessed in OSeac, and all of them reach statistical significance for prognosis in OSeac as expected, indicating the good performance of OSeac in prognostic biomarker screening. OSeac could also be used to screen novel prognosis biomarker for EAC, for example, RAP1B contributes to tumor malignant behavior and poor prognosis in GC (24). Using OSeac to assess the prognostic value of RAP1B in EAC, we found that RAP1B is a potential unfavorable prognostic indicator for EAC patients.…”

“…In addition, to further test the prediction power of OSeac, we choose a known prognostic marker of gastric cancer (GC) (24) to analyze it in OSeac. We examined prognostic potency of RAP1B for EAC patients by OSeac, and found that RAP1B was significantly associated with unfavorable OS in TCGA (P = 0.0464, HR: 2.0045, 95% CI: 1.0111-3.9741), GSE13898 (P = 0.0241, HR: 3.0920, 95% CI: 1.1596-8.2446) and GSE19417 (P = 0.0138, HR: 2.4119, 95% CI: 1.1965-4.8618).…”

Expression of ribosomal and actin network proteins and immunochemotherapy resistance in diffuse large B cell lymphoma patients

“…Of these 442 proteins, 102 ( t ‐test <0·05) and 20 (B‐H adjusted t ‐test P < 0·05) proteins were differentially expressed between the two patient groups (all 102 are listed in Table SII) (Fig ). Sixty‐five proteins were overexpressed in the REF/REL group and several of these proteins (Elongation factor 1‐beta, 14‐3‐3 protein gamma, nucleophosmin 1, RAP1B, Heat shock protein 60 and IMP dehydrogenase 2) have previously been described as negative prognostic factors or involved in drug resistance in other malignancies (De Bortoli et al , ; Li et al , ; Raungrut et al , ; Zhou et al , ; Yang et al , ; Sawazaki et al , ). Two proteins overexpressed in the REF/REL group have been reported as a negative prognostic marker or associated with multidrug resistance in DLBCL: Y‐box protein 1 (Miao et al , ) and pontin/RuvBL1 protein (Nishiu et al , ).…”